VENOOCCLUSIVE DISEASE OF THE LIVER INDUCED BY LOW-DOSE CYCLOPHOSPHAMIDE

A 2-yr-old child with idiopathic pulmonary hemosiderosis and autoimmun e thrombocytopenia developed hepatic veno-occlusive disease after bein g treated with long-term, low-dose cyclophosphamide, The authors belie ve that the injury was induced by cyclophosphamide. Although transplan t dosages of cyclophosphamide alone or in conjunction with other drugs have been shown to induce hepatic venocclusive disease, this is the f irst case of hepatic venocclusive disease associated with nontransplan t dosages of cyclophosphamide. Histopathologically, the injury was cha racterized by occlusive lesions of intrahepatic veins, both the termin al hepatic venules and portal veins branches, together with necrosis ( predominately involving Zones 3 and 2) and hemorrhages. An added risk factor could have been release of platelet-derived growth factor that in turn activated and promoted proliferation of fibroblasts and smooth muscle cells in the vessels, Previously reported cases of cyclophosph amide-related injury are reviewed.